This program project will examine mechanisms and consequences of the inflammatory effects of infection caused by chlamydial and gonococcal infection in the evolution of pelvic inflammatory disease (PID). A second theme will examine the possibility that transmission of these infections might be interrupted by beneficial immune factors. Support for 5 projects will be provided by 4 cores: Administrative, Clinical, Statistical and Pathologic. In Project 1, Dr. Rice will define the "natural history" of endometritis in women treated for uncomplicated cervicitis. This project will also examine the rate of healing in women treated with more intensive therapy. In Project 2, Drs. Zhang and Finberg will identify B and T cell epitopes of chlamydial major outer membrane protein (MOMP) that are protective in experimental and human infection. Components of chlamydial heat shock protein (hsp-60) that induce cell mediated immunity, particularly delayed by hypersensitivity in experimental systems, will also be defined. In Project 3, Dr. Golenbock will characterize chlamydial lipopolysaccharide (biological activity, regulation of response, chemical structure of lipid A), MOMP and hsp-60 as a stimulus for cytokine and prostaglandin release by monocytes, enhanced superoxide production and CR3 expression in polymorphonuclear leukocytes. Interactions of Chlamydia with CD11/CD18 leukocyte integrins will also be examined. In Project 4, Dr. Blake will examine the gonococcus' ability to engage in bidirectional adherence to cells in the female genital tract. Gonococcal opacity proteins II (PII) and lipooligosaccharides (LOSs) are involved in this adherence. Binding of PIII and LOS via asialoparagloboside residues and asialoglycoprotein receptors respectively, and regulation of these receptors will be measured in situ (clinical specimens) and in organ culture models developed by Dr. Apicella. In Project 5, Drs. Sharon and Rice will use a gonococcal LOS derived oligosaccharide (OS) conserved epitope as a vaccine candidate in the form of a chimeric (mouse/human) anti-idiotype antibody. The anti-idiotype will be modified by site-directed mutagenesis to improve its immunogenicity and will be tested for its ability to stimulate functional human-like anti-LOS antibody in severe combined immunodeficiency mice reconstituted with human peripheral blood leukocytes (HG-PBL-SCID).